Our objective is the evaluation of changes in the blood-retinal barrier in clinical experimental diabetes mellitus. The normally intact blood-retinal barrier prevents the passage of intravenous fluorescein into the vitreous. This can be documented by placing a corneal contact lens and using a slit-lamp fluorophotometer to accurately measure the intraocular concentration of fluorescein. In experimental and human diabetes mellitus there is an early breakdown of this blood-retinal barrier with passage of fluorescein from the retinal vascular tree into the vitreous. Animals will be studied before and after Streptozotocin-induced diabetes mellitus. Various methods of control and normalization of the blood sugar will be evaluated. The time course of the breakdown of the blood-retinal barrier will be evaluated as well as its susceptibility to normalization with insulin at the various periods of experimental diabetes. Long-term human studies are planned to evaluate the functional retinal microangiopathy detected by vitreous fluorophotometery. Various forms of therapy will be evaluated for their efficacy in reversing this functional microangiopathy. Correlation will be done with peripheral basement membrane thickness studies and functional microangiopathy detectable in the retinal vasculature.